Hydrogen Bromide → HCID 66732671, compound

HRID 1963415Notes

Reaction equation

HRID 1963415 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C@@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2C(OC)=O)=[C:4]([F:24])[CH:3]=1.Br>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][C@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][NH:9]2)=[C:4]([F:24])[CH:3]=1

Participants

3

Reactant 2

HCID 260Hydrogen BromideHCID 66732519HCID 66732519, compound

Product 1

HCID 66732671HCID 66732671, compoundYield 22%

Procedure

(2S,4S)-methyl 2-(4-chloro-2-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.45 g, 1.27 mmol) was dissolved in hydrogen bromide (33% in acetic acid, 10.00 mL, 57.08 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm) to yield 5-(trans-2-(4-chloro-2-fluorophenyl)piperidin-4-yl)isoxazol-3(2H)-one (82 mg, 22%). 1H NMR (400 MHz, dmso) δ 1.66-1.77 (m, 1H), 1.77-1.90 (m, 1H), 1.92-2.00 (m, 1H), 2.02-2.10 (m, 1H), 2.63-2.79 (m, 1H), 2.88-2.97 (m, 1H), 3.03-3.86 (omitted signals), 3.95 (d, 1H), 5.88 (s, 1H), 7.27 (dd, 1H), 7.35 (dd, 1H), 7.56 (t, 1H). HRMS Calcd for [C14H14ClFN2O2+H]+: 297.0806. Found: 297.0806.

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by preparative HPLC (Instrument: FractionLynx II, Mobilphase: gradient 5-95% MeCN in 0.2% NH3, pH 10, Column: Xbridge Prep C18 5 μm OBD 19*150 mm)

Sources & evidence

ORD record
ord-d9adb059a0e042cf815a71a63f34db9e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…